Rheumatoid arthritis Jyseleca is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Jyseleca may be used as monotherapy or in combination with methotrexate (MTX). Ulcerative colitis Jyseleca is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic agent.

Treatment with filgotinib should be initiated by a physician experienced in the treatment of rheumatoid arthritis or ulcerative colitis. Posology Rheumatoid arthritis The recommended dose of filgotinib for adult patients is 200 mg once daily. Ulcerative colitis The recommended dose for induction and maintenance treatment is 200 mg once daily. For patients with ulcerative colitis who do not show an adequate therapeutic benefit during the initial 10 weeks of treatment, 12 additional weeks of induction treatment with filgotinib 200 mg once daily may provide additional relief of symptoms (see section 5.1). Patients who have not shown any therapeutic benefit after 22 weeks of treatment should discontinue filgotinib. Laboratory monitoring, and dose initiation or interruption Guidance for laboratory monitoring, and dose initiation or interruption is provided in Table 1. Treatment should be interrupted if a patient develops a serious infection until the infection is controlled (see section 4.4). Table 1: Laboratory measures and monitoring guidance Laboratory measure Action Monitoring guidance Absolute neutrophil count (ANC) Treatment should not be initiated, or should be interrupted, if ANC is < 1 × 109 cells/L. Treatment may be restarted once ANC returns above this value Absolute lymphocyte count (ALC) Treatment should not be initiated, or should be interrupted, if ALC is < 0.5 × 109 cells/L. Treatment may be restarted once ALC returns above this value Haemoglobin (Hb) Treatment should not be initiated, or should be interrupted, if Hb is < 8 g/dL. Treatment may be restarted once Hb returns above this value Before treatment initiation and thereafter according to routine patient management Lipid parameters Patients should be managed according to international clinical guidelines for hyperlipidaemia 12 weeks after initiation of treatment and thereafter according to international clinical guidelines for hyperlipidaemia Special populations Elderly Rheumatoid arthritis A starting dose of 100 mg once daily is recommended for patients with rheumatoid arthritis aged 75 years and older as clinical experience is limited. Ulcerative colitis No dose adjustment is recommended for patients with ulcerative colitis up to 75 years of age. Filgotinib is not recommended in patients aged 75 years and older as there is no data in this population. Renal impairment No dose adjustment is required in patients with mild renal impairment (creatinine clearance [CrCl] = 60 mL/min). A dose of 100 mg of filgotinib once daily is recommended for patients with moderate or severe renal impairment (CrCl 15 to < 60 mL/min). Filgotinib has not been studied in patients with end stage renal disease (CrCl < 15 mL/min) and is therefore not recommended for use in these patients (see section 5.2). Hepatic impairment No dose adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh A or B). Filgotinib has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is therefore not recommended for use in these patients (see section 5.2). Paediatric population The safety and efficacy of filgotinib in children under the age of 18 years have not yet been established. No data are available. Method of administration Oral use. Jyseleca can be taken with or without food (see section 5.2). It has not been studied if tablets can be split, crushed, or chewed, and it is recommended that tablets are swallowed whole.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Active tuberculosis (TB) or active serious infections (see section 4.4). Pregnancy (see section 4.6).

Immunosuppressive medicinal products Combination of filgotinib with other potent immunosuppressants such as ciclosporin, tacrolimus, biologics or other Janus kinase (JAK) inhibitors is not recommended as a risk of additive immunosuppression cannot be excluded. Infections Infections, including serious infections, have been reported in patients receiving filgotinib. The most frequent serious infection reported with filgotinib was pneumonia (see section 4.8). Among opportunistic infections, TB, oesophageal candidiasis, and cryptococcosis were reported with filgotinib. The risks and benefits of treatment should be considered prior to initiating filgotinib in patients: • with chronic or recurrent infection • who have been exposed to TB • with a history of a serious or an opportunistic infection • who have resided or travelled in areas of endemic TB or endemic mycoses; or • with underlying conditions that may predispose them to infection. Patients should be closely monitored for the development of signs and symptoms of infections during and after filgotinib treatment. If an infection develops during treatment with filgotinib, the patient should be carefully monitored and filgotinib treatment should be temporarily interrupted if the patient is not responding to standard antimicrobial therapy. Filgotinib treatment may be resumed once the infection is controlled. As there is a higher incidence of serious infections in the elderly aged 75 years and older, caution should be used when treating this population. Tuberculosis Patients should be screened for TB before initiating filgotinib. Filgotinib should not be administered to patients with active TB (see section 4.3). In patients with latent TB, standard antimycobacterial therapy should be initiated before administering filgotinib. Patients should be monitored for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating treatment. Viral reactivation Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies (see section 4.8). In rheumatoid arthritis clinical studies, the risk of herpes zoster appeared to be higher in female patients, Asian patients, patients = 50 years of age, patients with a medical history of herpes zoster, patients with a medical history of chronic lung disease and patients treated with filgotinib 200 mg once daily. If a patient develops herpes zoster, filgotinib treatment should be temporarily interrupted until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed in accordance with clinical guidelines before starting and during treatment with filgotinib. Patients who were positive for both hepatitis C antibody and hepatitis C virus RNA were excluded from clinical studies. Patients who were positive for hepatitis B surface antigen or hepatitis B virus DNA were excluded from clinical studies. Malignancy The risk of malignancies is increased in patients with rheumatoid arthritis and ulcerative colitis. Immunomodulatory medicinal products may increase the risk of malignancies. The clinical data are insufficient to assess the potential incidence of malignancies following exposure to filgotinib. Long-term safety evaluations are ongoing. Malignancies were observed in clinical studies of filgotinib. The risks and benefits of filgotinib treatment should be considered prior to initiating treatment in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing filgotinib treatment in patients who develop a malignancy. Non-melanoma skin cancer NMSCs have been reported in patients treated with filgotinib. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Haematological abnormalities ANC < 1 × 109 cells/L (see section 4.8) and ALC < 0.5 × 109 cells/L were reported in = 1% of patients in the rheumatoid arthritis clinical studies and in < 3% of patients in the ulcerative colitis clinical studies. Treatment should not be initiated, or should be temporarily interrupted, in patients with an ANC < 1 × 109 cells/L, ALC < 0.5 × 109 cells/L or haemoglobin < 8 g/dL observed during routine patient management (see section 4.2). Vaccinations Use of live vaccines during, or immediately prior to, filgotinib treatment is not recommended. It is recommended that immunisations, including prophylactic zoster vaccinations, be updated in agreement with current immunisation guidelines prior to initiating filgotinib treatment. Lipids Treatment with filgotinib was associated with dose-dependent increases in lipid parameters, including total cholesterol, and high-density lipoprotein (HDL) levels, while low-density lipoprotein (LDL) levels were slightly increased (see section 4.8). LDL cholesterol returned to pre-treatment levels in the majority of patients who started statin therapy while taking filgotinib. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined (see section 4.2 for monitoring guidance). Cardiovascular risk Patients with rheumatoid arthritis and ulcerative colitis have an increased risk for cardiovascular disorders. Filgotinib should be used with caution in patients with cardiovascular risk factors. Patients should have risk factors (e.g., hypertension, hyperlipidaemia) managed as part of usual standard of care. Venous thromboembolism Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors including filgotinib. JAK inhibitors should be used with caution in patients with risk factors for DVT/PE, such as older age, obesity, a medical history of DVT/PE, or patients undergoing surgery, and prolonged immobilisation. If clinical features of DVT/PE occur, filgotinib treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment. Lactose content Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Effect of other medicinal products on filgotinib Filgotinib is primarily metabolised by carboxylesterase 2 (CES2), which can be inhibited in vitro by medicinal products such as fenofibrate, carvedilol, diltiazem or simvastatin. The clinical relevance of this

Women of childbearing potential / Contraception Women of childbearing potential have to use effective contraception during and for at least 1 week after cessation of filgotinib treatment. Pregnancy There are no or limited amount of data from the use of filgotinib in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Based on findings in animals, filgotinib may cause foetal harm and is therefore contraindicated during pregnancy (see section 4.3). Breast-feeding It is unknown whether filgotinib is excreted in human milk. A risk to breastfed newborns/infants cannot be excluded. Therefore, Jyseleca should not be used during breast-feeding. Fertility In animal studies, decreased fertility, impaired spermatogenesis, and histopathological effects on male reproductive organs were observed (see section 5.3). The data from two dedicated Phase 2 clinical studies (MANTA and MANTA RAy, n=240) to evaluate the human testicular safety in men with inflammatory arthritis diseases and inflammatory bowel diseases did not reveal a difference between treatment groups in the proportion of patients who had a 50% or more decrease from baseline in semen parameters at week 13 (pooled primary endpoint: filgotinib 6.7%, placebo 8.3%) and at week 26. Further, the data did not show any relevant changes in sex hormone levels or change from baseline in semen parameters across treatment groups. Overall, these clinical data were not suggestive of filgotinib-related effects on testicular function. Animal studies did not indicate effects with respect to fertility in females.

Filgotinib has minor influence on the ability to drive and use machines. Patients should be advised that dizziness and vertigo has been reported during treatment with Jyseleca (see section 4.8).

Summary of the safety profile Rheumatoid arthritis The most frequently reported adverse reactions are nausea (3.5%), upper respiratory tract infection (URTI, 3.3%), urinary tract infection (UTI, 1.7%), dizziness (1.2%) and lymphopenia (1.0%). Ulcerative colitis In general, the overall safety profile observed in filgotinib-treated patients with ulcerative colitis was generally consistent with the safety profile observed in patients with rheumatoid arthritis. Tabulated list of adverse reactions The following adverse reactions are based on clinical studies (Table 2). The adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: common (= 1/100 to < 1/10) and uncommon (= 1/1 000 to < 1/100). Table 2: Adverse reactions Frequency a Adverse reaction Infections and infestations Common Urinary tract infection (UTI) Upper respiratory tract infection (URTI) Uncommon Herpes zoster Pneumonia Sepsis Blood and lymphatic system disorders Common Lymphopenia Uncommon Neutropenia Metabolism and nutrition disorders Uncommon Hypercholesterolaemia Nervous system disorders Common Dizziness Ear and labyrinth disorders Uncommon Vertigo Frequency a Adverse reaction Gastrointestinal disorders Common Nausea Investigations Uncommon Blood creatine phosphokinase increased a Frequency based on placebo-controlled pre-rescue period (week 12) pooled across FINCH 1 and 2, and DARWIN 1 and 2, for patients with rheumatoid arthritis who received filgotinib 200 mg. Frequencies reported in the SELECTION study in patients with ulcerative colitis who received filgotinib 200 mg were generally consistent with those reported in the rheumatoid arthritis studies. Laboratory changes Creatinine An increase in serum creatinine occurred with filgotinib treatment. At week 24 in the Phase 3 studies (FINCH 1, 2, and 3), the mean (SD) increase from baseline in serum creatinine was 0.07 (0.12) and 0.04 (0.11) mg/dL for filgotinib 200 mg and 100 mg, respectively. Mean creatinine values remained within the normal range. Lipids Treatment with filgotinib was associated with dose-dependent increases in total cholesterol and HDL levels, while LDL levels were slightly increased. LDL/HDL ratios were generally unchanged. Lipid changes were observed within the first 12 weeks of filgotinib treatment and remained stable thereafter. Serum phosphate Generally mild, transient or intermittent, and dose-dependent decreases in serum phosphate levels occurred during treatment with filgotinib and resolved without discontinuation of treatment. At week 24 in the Phase 3 studies (FINCH 1, 2, and 3), serum phosphate values of less than 2.2 mg/dL (the lower limit of normal) were reported in 5.3% and 3.8% of subjects receiving filgotinib 200 mg and 100 mg, respectively; no values below 1.0 mg/dL were reported. In placebo-controlled Phase 3 studies with background DMARDs (FINCH 1 and FINCH 2) through 12 weeks, serum phosphate levels of less than 2.2 mg/dL were reported in 1.6%, 3.1%, and 2.4% in the placebo, filgotinib 200 mg, and filgotinib 100 mg groups, respectively. Description of selected adverse reactions Infections Rheumatoid arthritis In placebo-controlled studies with background DMARDs (FINCH 1, FINCH 2, DARWIN 1, and DARWIN 2), the frequency of infection over 12 weeks in the filgotinib 200 mg group was 18.1% compared to 13.3% in the placebo group. In the MTX-controlled study FINCH 3, the frequency of infection over 24 weeks in the filgotinib 200 mg monotherapy and filgotinib 200 mg plus MTX groups was 25.2% and 23.1%, respectively, compared to 24.5% in the MTX group. The overall exposure-adjusted incidence rate (EAIR) of infections for the filgotinib 200 mg group across all seven Phase 2 and 3 clinical studies (2,267 patients) was 26.5 per 100 patient-years of exposure (PYE). In placebo-controlled studies with background DMARDs, the frequency of serious infection over 12 weeks in the filgotinib 200 mg group was 1.0% compared to 0.6% in the placebo group. In the MTX-controlled study FINCH 3, the frequency of serious infection over 24 weeks in the filgotinib 200 mg monotherapy and filgotinib 200 mg plus MTX groups was 1.4% and 1.0%, respectively, compared to 1.0% in the MTX group. The overall EAIR of serious infections for the filgotinib 200 mg group across all seven Phase 2 and 3 clinical studies (2,267 patients) was 1.7 per 100 PYE. The most common serious infection was pneumonia. The EAIR of serious infections remained stable with long-term exposure. In rheumatoid arthritis clinical studies, there was a higher incidence of serious infections in patients aged 65 years and older. In placebo-controlled studies with background DMARDs, the frequencies of infectious ADRs over 12 weeks for filgotinib 200 mg compared to placebo were: URTI (3.3% versus 1.8%), UTI (1.7% versus 0.9%), pneumonia (0.6% versus 0.4%), and herpes zoster (0.1% versus 0.3%). Most of the herpes zoster events involved a single dermatome and were non-serious. The overall EAIR of herpes zoster across all seven Phase 2 and 3 clinical studies (2 267 and 1 647 total patients for 200 mg and 100 mg, respectively) was 1.6 and 1.1 per 100 PYE in the 200 mg group and 100 mg group, respectively. Ulcerative colitis The types of serious infections in the ulcerative colitis clinical studies were generally similar to those reported in the rheumatoid arthritis clinical studies with filgotinib monotherapy treatment groups. Across the two placebo-controlled induction studies, the frequency of serious infections was 0.6% in the filgotinib 200 mg group, 1.1% in the filgotinib 100 mg group, and 1.1% in the placebo group. In the placebo-controlled maintenance study, the frequency of serious infections in the filgotinib 200 mg group was 1%, compared to 0% in the respective placebo group. In the maintenance study filgotinib 100 mg group, the frequency of serious infections was 1.7%, compared with 2.2% in the respective placebo group. Opportunistic infections (excluding TB) In rheumatoid arthritis placebo-controlled studies with background DMARDs, there were no opportunistic infections over 12 weeks in the filgotinib 200 mg group or the placebo group. In the MTX-controlled study FINCH 3, the frequency of opportunistic infections over 24 weeks was 0, 0.2%, and 0 in the filgotinib 200 mg monotherapy, filgotinib 200 mg plus MTX, and MTX groups, respectively. The overall EAIR of opportunistic infections for the filgotinib 200 mg group across all seven Phase 2 and 3 rheumatoid arthritis clinical studies (2 267 patients) was 0.1 per 100 PYE. Nausea Nausea was generally transient and reported during the first 24 weeks of filgotinib treatment. Creatine phosphokinase Dose-dependent increases in creatine phosphokinase (CPK) occurred within the first 12 weeks of filgotinib treatment and remained stable thereafter. At week 24 in the Phase 3 studies (FINCH 1, 2, and 3), the mean (SD) increase from baseline in CPK was -16 (449), 61 (260), and 33 (80) U/L for placebo, filgotinib 200 mg and 100 mg, respectively. In placebo-controlled Phase 3 studies with background DMARDs (FINCH 1 and FINCH 2) through 12 weeks, CPK elevations > 5 × upper limit of normal (ULN) were reported in 0.5%, 0.3%, and 0.3% of patients in the placebo, filgotinib 200 mg, and filgotinib 100 mg groups, respectively. Most elevations > 5 × ULN did not require treatment discontinuation. Experience from long-term extension studies Rheumatoid arthritis In the long-term extension study DARWIN 3, patients enrolled from DARWIN 1 (N = 497) received filgotinib once a day for a median duration of 5.3 years and patients enrolled from DARWIN 2 (N = 242) received filgotinib once a day for a median duration of 5.6 years. In the long-term extension study FINCH 4, 1 530 patients received filgotinib 200 mg once daily and 1 199 patients received filgotinib 100 mg once daily for a median duration of 1.5 years. The safety profile of filgotinib was similar to that in the Phase 2 and Phase 3 studies. Ulcerative colitis In the long-term extension study (SELECTION LTE) in patients who participated in the SELECTION study, patients received filgotinib 200 mg (N = 871), filgotinib 100 mg (N = 157), or placebo (N = 133) for median durations of 55, 36, and 32 weeks, respectively. The safety profile of filgotinib was similar to that in the SELECTION induction and maintenance studies. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

Filgotinib has been administered in clinical studies following single and once daily administration up to 450 mg without dose-limiting toxicity. Adverse reactions were comparable to those seen at lower doses and no specific toxicities were identified. Pharmacokinetic data following a single dose of 100 mg filgotinib in healthy subjects indicate that approximately 50% of the administered dose is eliminated within 24 hours of dosing and 90% of the dose is eliminated within 72 hours. In case of an , it is recommended that a patient be monitored for signs and symptoms of adverse reactions. Treatment of with filgotinib consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. It is unknown whether filgotinib can be removed by dialysis.

Pharmacotherapeutic group: Immunosuppressants, Janus-associated kinase (JAK) inhibitors, ATC code: L04AF04 Mechanism of action Filgotinib is an adenosine triphosphate (ATP)-competitive and reversible inhibitor of the JAK family. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor

Absorption Following oral administration, filgotinib was absorbed quickly and its median peak plasma concentration was observed 2 to 3 hours postdose after multiple dosing; the median peak plasma concentrations of its primary metabolite GS-829845 were observed 5 hours postdose after multiple dosing. Filgotinib and GS-829845 exposures (AUC) and Cmax were similar in healthy adult subjects and patients with rheumatoid arthritis and ulcerative colitis. Filgotinib and GS-829845 exposures (AUC) and Cmax are dose-proportional over the therapeutic dose range. Steady-state concentrations of filgotinib are achieved in 2 - 3 days with negligible accumulation after once daily administration. Steady-state concentrations of GS-829845 are achieved in 4 days with approximately 2-fold accumulation after once daily dosing of filgotinib. There were no clinically relevant differences in exposures when filgotinib was administered with a high-fat or low-fat meal as compared to a fasted state. Filgotinib can be administered with or without food. Steady-state exposures of filgotinib and GS-829845 are provided in Table 8. Table 8: Multiple dose pharmacokinetic parameters of filgotinib and GS-829845 following oral administration of filgotinib 200 mg with or without food in patient populations Rheumatoid arthritis a Ulcerative colitis b Parameter Mean (%CV) Filgotinib c GS-829845 d Filgotinib GS-829845 Cmax (µg/mL) 2.15 (48.1) 4.43 (29.3) 2.12 (50.3) e 4.02 (30.5) e AUCtau (µg•h/mL) 6.77 (43.7) 83.2 (27.3) 6.15 (28.1) f 72.1 (33.9) g CV: coefficient of variation. a From intensive PK analyses of studies FINCH 1, FINCH 2, and FINCH 3 in rheumatoid arthritis patients receiving 200 mg filgotinib once daily. b From intensive PK analysis of SELECTION study in ulcerative colitis patients receiving 200 mg filgotinib once daily. c N = 37 d N = 33 e N = 13 f N = 12 g N = 11 Distribution Filgotinib and GS-829845 binding to human plasma proteins is low (55 - 59% and 39 - 44% bound, respectively). The blood-to-plasma ratio of filgotinib ranged from 0.85 to 1.1 indicating no preferential distribution of filgotinib and GS-829845 into blood cells. Filgotinib and GS-829845 are substrates of the P-gp transporter. Biotransformation Filgotinib is extensively metabolised with approximately 9.4% and 4.5% of an orally administered dose recovered as unchanged filgotinib in urine and faeces, respectively. Filgotinib is primarily metabolised by CES2, and to a lesser extent by CES1. Both CES2 and CES1 form GS-829845, an active circulating metabolite that is approximately 10-fold less potent than the parent compound. In a clinical pharmacology study, filgotinib and GS-829845 accounted for the majority of radioactivity circulating in plasma (2.9% and 92%, respectively). No other major metabolites were identified. As both filgotinib and GS-829845 contribute to efficacy, their exposures were combined into a single parameter, AUCeff. AUCeff is the sum of the AUC of filgotinib and GS-829845, corrected for their respective molecular weights and potencies. Elimination Approximately 87% of the administered dose was eliminated in the urine as filgotinib and its metabolites, while about 15% of the dose was eliminated in the faeces. GS-829845 accounted for approximately 54% and 8.9% of dose recovered in urine and faeces, respectively. The mean terminal half-lives of filgotinib and GS-829845 were approximately 7 and 19 hours, respectively. Other special populations Weight, gender, race, and age Bodyweight, gender, race, and age did not have a clinically relevant effect on the pharmacokinetics (AUC) of filgotinib or GS-829845. Elderly There were no clinically relevant differences in mean filgotinib and GS-829845 exposures (AUC and Cmax) between older patients aged = 65 years relative to adult patients aged < 65 years. Renal impairment The pharmacokinetics of filgotinib and GS-829845 were unaffected in subjects with mild renal impairment (CrCl 60 to < 90 mL/min). Increases in exposures (AUC) of filgotinib, GS-829845, and combined AUCeff (= 2-fold), were observed in subjects with moderate renal impairment (CrCl 30 to < 60 mL/min). In subjects with severe renal impairment (CrCl 15 to < 30 mL/min), filgotinib exposure (AUC) increased by 2.2-fold and GS-829845 exposure significantly increased by 3.5-fold leading to a 3-fold increase in AUCeff. The pharmacokinetics of filgotinib has not been studied in subjects with end stage renal disease (CrCl < 15 mL/min). Hepatic impairment No clinically relevant changes in the exposures (AUC) of filgotinib and GS-829845 individually, or their combined exposure (AUCeff), were observed in subjects with moderate hepatic impairment (Child-Pugh B). The pharmacokinetics of filgotinib has not been studied in subjects with severe hepatic impairment (Child-Pugh C). Effect of filgotinib on other medicinal products Potential

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology. The carcinogenic potential of filgotinib was evaluated in a 6-month rasH2 transgenic mouse study and a 2-year rat study. Filgotinib was not carcinogenic in mice at up to 150 mg/kg/day, which resulted in exposures of approximately 25 and 12 times the exposures in humans at the 100 mg and 200 mg once daily doses, respectively. In the 2-year rat study, filgotinib treatment resulted in an increase in incidence and decrease in latency of benign Leydig cell tumours at the highest dose of 45 mg/kg/day (exposures of approximately 4.2 times exposures in humans at the 200 mg once daily dose); the clinical relevance of this finding is low. Filgotinib was not mutagenic or clastogenic in the in vitro bacterial reverse mutation assay, in vitro chromosome aberration assay, and in vivo rat micronucleus assay. Adverse findings of degeneration/necrosis of incisor ameloblasts were observed in rats at exposures 21- to 28-fold greater than clinical exposures at the 200 mg filgotinib dose, with exposure margins at the no-observed-adverse-effect-level (NOAEL) ranging from 3.5- to 8-fold. The human relevance of these dental findings is considered low since in contrast to adult patients, ameloblasts in rats persist into adulthood to support lifelong continuous incisor growth. Impaired spermatogenesis and histopathological effects on male reproductive organs (testes and epididymis) were observed with filgotinib in rats and dogs. At the NOAELs in dogs (the most sensitive species), the exposure margin is 2.7-fold at the 200 mg once daily dose in humans. The severity of the histological effects was dose-dependent. Spermatogenic and histopathological effects were not fully reversible at exposure margins of approximately 7- to 9-fold the exposure at the 200 mg once daily dose in humans. Embryo-foetal development studies in rats and rabbits demonstrated embryolethality and teratogenicity at exposures comparable to 200 mg filgotinib once daily dosing in humans. Visceral and skeletal malformations and/or variations were observed at all dose levels of filgotinib. Filgotinib was administered to pregnant rats at doses of 25, 50, and 100 mg/kg/day. Dose-related increases in the incidence of internal hydrocephaly, dilated ureters, and multiple vertebral anomalies were seen at all dose levels. At 100 mg/kg/day, an increased number of early and late resorptions were noted together with a decreased number of viable foetuses. In addition, foetal body weights were decreased. In rabbits, filgotinib caused visceral malformations mainly in the lungs and cardiovascular system, at a dose level of 60 mg/kg/day. Filgotinib caused skeletal malformations affecting the vertebral column region at dose levels of 25 and 60 mg/kg/day, mainly in vertebra, ribs and sternebrae. Fused sternebrae also occurred at 10 mg/kg/day filgotinib. Retarded skeletal ossification was evidenced at 60 mg/kg/day. No adverse effects on pre-/postnatal development were observed in rats in a pre- and postnatal development study of filgotinib and GS-829845. Filgotinib and GS-829845 were detected in nursing rat pups after administration of filgotinib to lactating female rats from gestation day 6 through 10 days post-partum at dose levels of 2, 5, and 15 mg/kg/day, likely due to the presence of filgotinib in milk. At the highest tested dose, maternal systemic exposure (AUC) to filgotinib in rats was approximately 2 times the exposure in humans at the 200 mg once daily dose; exposures in nursing pups were less than 6% that of maternal exposure on day 10 post-partum. Due to the low exposure of the animals, the pre-/postnatal development study was considered inconclusive.

Tablet core Microcrystalline cellulose Lactose monohydrate Pregelatinised starch Colloidal silicon dioxide Fumaric acid Magnesium stearate Film-coating Polyvinyl alcohol Titanium dioxide (E171) Macrogol Talc Iron oxide yellow (E172) Iron oxide red (E172)

Not applicable.

4 years

Store in the original package in order to protect from moisture. Keep the bottle tightly closed.

White, high-density polyethylene (HDPE) bottles, enclosed with a child-resistant polypropylene (PP) screw cap lined with an induction-sealed aluminium foil liner. Each bottle contains either a canister or sachet containing silica gel desiccant and polyester coil. The following pack sizes are available: outer cartons containing 1 bottle of 30 film-coated tablets and outer cartons containing 90 (3 bottles of 30) film-coated tablets. Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements

Feb. 16, 2026

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